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TIP60 inhibitors – therapy for Irritable Bowel Disease (IBD); ulcerative colitis and Crohn’s diseases

Description:

 

Inhibitors of TIP60, maintaining regulatory T cells (Tregs) and ameliorating autoimmune diseases.

 

Problem

Inflammatory bowel disease (IBD) involves chronic inflammation of all or part of digestive tract. IBD includes ulcerative colitis and Crohn’s disease both very prevalent and known to cause severe complications and discomfort.

Inhibitors of TIP60, a histone acetyltransferase, have been developed to maintain peripheral Treg cells, further enabling them to ameliorate autoimmune diseases. Preliminary animal studies have focused on the treatment of colitis, but these compounds are expected to find application in a wide variety of autoimmune disorders.  

 

Solution

Dr. Greene’s laboratory synthesized small molecules that bind and modulate TIP60 acetyltransferase activity. Lead compounds tested bind to TIP60’s non-active site while maintaining its scaffolding ability. As a result, TIP60 binds FOXP3 and recruits p300, leading to FOXP3’s increased overall transcriptional activity and positive regulation of Treg cells. Since the deficiency or dysfunction of Treg cells has been linked to several autoimmune and inflammatory diseases including IBD, increasing their function through functional inhibition of TIP60 directly points to potential therapeutic approach. 

 

Advantages

• TIP60 inhibition as a novel pathway to treat for autoimmune diseases.

• Potential therapy for a wide range of therapies as TIP60 is involved in mediating activities of T regulatory cells, which in turn play an important role in autoimmune and inflammatory diseases.

 

 

Applications

• In vivo animal data demonstrates POC efficacy in treating ulcerative colitis.  

 

Stage of Development

• Animal studies have been completed and positive results reported where TIP60 inhibitor therapy reversed weight loss, blood in the stool and diarrhea, as well as maintained colon length.

 

Intellectual Property

USSN 9,701,631 

Reference Media

• Xiao, Y. et al.; Cell Rep. 2014 Jun 12;7(5):1471

• Zhang, H. et al.; Immunol Cell Biol. 2012 Jan;90(1):95

 

Desired partnerships

•  License

 

Docket #  X5743 

 

 

Download PDF

 

 


Patent Information:
For Information, Contact:
Viviane Martin
Director, PSOM Licensing Group
University of Pennsylvania
215-746-4275
martinv@upenn.edu
Inventors:
Mark Greene
Keywords:
Biotechnology